Rostral anterior cingulate cortex activity and early symptom improvement during treatment for major depressive disorder.

1Labrotory of Brain, Behavior, and Pharmacology, and the UCLA Depression Research for Clinic Program, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA. alexkorb@ucla.edu

Abstract

In treatment trials for major depressive disorder (MDD), early symptom improvement is predictive of eventual clinical response. Clinical response may also be predicted by elevated pretreatment theta (4-7Hz) current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC). We investigated the relationship between pretreatment EEG and early improvement in predicting clinical outcome in 72 MDD subjects across three placebo-controlled treatment trials. Subjects were randomized to receive fluoxetine, venlafaxine, or placebo. Theta current density in the rACC and mOFC was computed with Low-Resolution Brain Electromagnetic Tomography (LORETA). An analysis of covariance examining week-8 Hamilton Depression Rating Scale (HamD) percent change, showed a significant effect of week-2HamD percent change, and a significant three-way interaction of week-2HamD percent change×treatment×rACC. Medication subjects with robust early improvement showed almost no relationship between rACC theta current density and final clinical outcome. However, in subjects with little early improvement, rACC activity showed a strong relationship with clinical outcome. The model examining the mOFC showed a trend in the three-way interaction. A combination of pretreatment rACC activity and early symptom improvement may be useful for predicting treatment response.

Lines indicate the average marginal effects of rACC theta current density (centered) on Week 8 HamD percent change at different levels of early improvement. That is, the lines reflect the expected relationship between rACC theta current density and outcome at a given degree of early improvement. Medication subjects with robust early improvement (e.g. 50%) show a weak relationship between rACC theta current density and clinical outcome, while medication subjects with little to no early improvement (e.g. 0%) show a strong relationship between rACC theta current density and clinical outcome.